Biochemical And Biophysical Research Communications[JOURNAL]
Sun
200 papers
The protein turnover and trafficking of Chlamyopsin6 is regulated by IFT88 and IFT52 in the Chlamydomonas reinhardtii.
Sushmita K, Sharma S, Singh R … +1 more , Kateriya S
Biochem Biophys Res Commun · 2026 Aug · PMID 42214917 · Publisher ↗
Microbial rhodopsin-based optogenetics has been widely applied to diverse mammalian and plant cell types for controlling membrane potential mediated responses. Microbial rhodopsin fusions like RhoPDE, and RhoGC (enzyme r...
Microbial rhodopsin-based optogenetics has been widely applied to diverse mammalian and plant cell types for controlling membrane potential mediated responses. Microbial rhodopsin fusions like RhoPDE, and RhoGC (enzyme rhodopsins) have also been used for spatiotemporal modulation of cyclic nucleotide signaling non-invasively across the biological systems. Complex microbial rhodopsins like Chlamyopsin5 and Chlamyopsin6 are modular in nature and rhodopsin is coupled with the two-component signaling module (histidine kinase and response regulator), and cyclase domain in a tandem. However, functional characterization and cellular trafficking of these optogenetically active proteins to the desired subcellular organelle is still a major concern in optogenetics field. Current study is focused on the trafficking of two of the complex microbial modular rhodopsins (Chalmyopsin5 and Chlamyopsin6) in a green alga, Chlamydomonas reinhardtii. Immunolocalization of Chlamyopsin5 and Chlamyopsin6 in wild strain suggests their differential subcellular localization; Chlamyopsin5 is mainly in eyespot and Chlamyopsin6 is localized both in flagella and eyespot. Extensive immunocytochemistry of Chlamyopsin5 and Chlamyopsin6 was performed in different intraflagellar transport (IFT) components-defective strains of Chlamydomonas to dissect their trafficking and localization. Our results indicated the trafficking of Chlamyopsin5 to the eyespot is independent of IFT machinery while IFT machinery drives localization of Chlamyopsin6 to the flagella. Further, we demonstrate that IFT88 and IFT52 stabilizes turnover of Chlamyopsin6 and IFT20 interacts with Chlamyopsin6 in Chlamydomonas. Collectively, our study enabled us to understand the targeting of large Chlamyopsins to the subcellular compartment (eyespot and flagella). This study pave way to expand optogenetic applications of these complex microbial-type modular rhodopsins for opto-modulation of two-components mediated physiological processes.
Cryo-EM structures of GPR133 from basal organisms elucidate evolutionary conservation and divergence of its activation.
Wang MX, Wang J, Yang DX … +5 more , Rong J, Yang Z, Xiao P, Ping YQ, Sun JP
Biochem Biophys Res Commun · 2026 Aug · PMID 42214916 · Publisher ↗
Adhesion G protein-coupled receptor GPR133 participates extensively in bone development, skeletal muscle function regulation, and the malignant progression of glioma. This receptor is activated through a Stachel sequence...
Adhesion G protein-coupled receptor GPR133 participates extensively in bone development, skeletal muscle function regulation, and the malignant progression of glioma. This receptor is activated through a Stachel sequence-dependent mechanism and mediates downstream Gs signaling. However, the evolutionary conservation of this activation mechanism and its structural basis remain unclear, particularly in basal organisms. Here, we show that GPR133 from the cephalochordate Branchiostoma lanceolatum and the mollusk Mytilus coruscus exhibits constitutive Gs signaling activity. We further determined the cryo-EM structures of Branchiostoma lanceolatum GPR133-Gs complex and Mytilus coruscus GPR133-Gs complexes at resolutions of 2.92 Å and 2.71 Å, respectively. Cross-species structural comparisons reveal differences in the Stachel binding pocket, overall conformation and Gs coupling interface, providing structural insights into the evolutionary conservation and diversification of Stachel-dependent activation in aGPCRs.
A novel model of central precocious puberty: differentiation of patient-derived induced pluripotent stem cells into GnRH neurons.
Lin Y, Guo J, Fan T … +2 more , Yu J, Sun W
Biochem Biophys Res Commun · 2026 Aug · PMID 42208232 · Publisher ↗
Central precocious puberty (CPP) is a pediatric endocrine disorder characterized by the premature activation of hypothalamic gonadotropin-releasing hormone (GnRH) neurons. At present, CPP researches predominantly rely on...
Central precocious puberty (CPP) is a pediatric endocrine disorder characterized by the premature activation of hypothalamic gonadotropin-releasing hormone (GnRH) neurons. At present, CPP researches predominantly rely on animal models, which cannot fully recapitulate the endocrine properties of human GnRH neurons. Herein, we aimed to generate GnRH neurons from induced pluripotent stem cells (iPSCs) derived from the peripheral blood of CPP patient, thereby establishing a novel human cell-based model of CPP. Using a classical three-step in vitro differentiation protocol, iPSCs from both CPP patient and healthy adult females (serving as the healthy control (HC) group) were differentiated into GnRH neurons. Quantitative real-time polymerase chain reaction, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were employed to assess the expression of GNRH1 and microtubule-associated protein 2 (MAP2), as well as the secretion levels of GnRH and γ-aminobutyric acid (GABA). At day 27, 28 and 29, GnRH neurons derived from the CPP group exhibited significantly elevated GNRH1 mRNA levels, along with higher fluorescence intensities of GNRH1 and MAP2 compared to those from the HC group. ELISA further demonstrated that GnRH concentrations in CPP were significantly higher at all examined time points compared with the HC group. In contrast, GABA concentrations were reduced in CPP. These findings indicated that CPP patient-derived GnRH neurons displayed intrinsically accelerated maturation and GnRH hypersecretion, accompanied by attenuated GABAergic inhibitory function. Together, this study has successfully established a CPP cell model based on iPSCs derived from CPP patient, providing a novel experimental platform for in-depth exploration of the pathogenesis and drug intervention for CPP in the future.
Tamoxifen promotes myogenic differentiation and skeletal muscle regeneration via activation of the GRP94.
Xing L, Zhang K, Han Y … +3 more , Teng H, Wang Y, Li S
Biochem Biophys Res Commun · 2026 Aug · PMID 42208231 · Publisher ↗
Efficient skeletal muscle repair remains a significant clinical challenge due to the lack of safe pharmacological interventions. Our work identifies Tamoxifen as a potent driver of muscle regeneration, operating through...
Efficient skeletal muscle repair remains a significant clinical challenge due to the lack of safe pharmacological interventions. Our work identifies Tamoxifen as a potent driver of muscle regeneration, operating through the GRP94. In C2C12 myoblasts, Tamoxifen treatment directly triggered myogenic differentiation and accelerated myotube formation in a dose-dependent manner, alongside the marked upregulation of MyoD, Myogenin (MyoG), and MYHC. These pro-myogenic effects were effectively abolished upon GRP94 inhibition, confirming its role as an essential mediator. In vivo, using a bupivacaine-induced injury model, we observed that 10 mg/kg Tamoxifen significantly expedited tissue repair and increased the cross-sectional area (CSA) of regenerating myofibers. Collectively, our findings demonstrate for the first time that Tamoxifen orchestrates muscle repair by modulating GRP94, offering a promising strategy for treating acute injury and chronic muscle wasting.
Structural insights into the ligand and G protein recognition by P2YR.
Oshima HS, Akasaka H, Sano FK … +1 more , Nureki O
Biochem Biophys Res Commun · 2026 Aug · PMID 42208230 · Publisher ↗
P2Y purinergic receptors are GPCRs that recognize extracellular nucleotides to mediate diverse physiological processes. Among 12-like subfamily members, P2YR has well-documented roles in neuroprotection and cholesterol m...
P2Y purinergic receptors are GPCRs that recognize extracellular nucleotides to mediate diverse physiological processes. Among 12-like subfamily members, P2YR has well-documented roles in neuroprotection and cholesterol metabolism. Notably, P2YR displays robust activity toward the G pathway in addition to its canonical G coupling, yet the structural basis for its ligand recognition and G protein selectivity has remained unclear. Here, we present the cryo-EM structure of the P2YR-G complex bound to ADP at a resolution of 2.83 Å. The structure reveals the distinctive ligand recognition mechanism of P2YR, in which an N-terminal arginine caps the orthosteric binding pocket. Furthermore, we also elucidated the structure of P2YR, which shows the lowest G activation ability among the 12-like P2Y receptors, in complex with UDP and G at a resolution of 2.93 Å. Structural comparison with the 12-like P2Y receptors implicates ICL2-mediated contacts with the Gα hydrophobic cavity as a key structural determinant of G selectivity. Together, these findings provide mechanistic insights into nucleotide signaling and a structural foundation for advancing structure-based approaches to targeting the 12-like P2Y receptors.
Dual lipid-modified Thioredoxin-h9 functions as a membrane-associated redox and DNA-interacting protein in Arabidopsis thaliana.
Park JH, Lee ES
Biochem Biophys Res Commun · 2026 Aug · PMID 42208229 · Publisher ↗
Thioredoxins (Trxs) are ubiquitous redox proteins that regulate intracellular thiol-disulfide balance and participate in diverse stress response in plants. Although several Arabidopsis h-type Trxs have been functionally...
Thioredoxins (Trxs) are ubiquitous redox proteins that regulate intracellular thiol-disulfide balance and participate in diverse stress response in plants. Although several Arabidopsis h-type Trxs have been functionally characterized, the molecular functional roles of Trx-h9 remain poorly understood. In this study, we investigated the molecular characteristics of Trx-h9 using comparative biochemical analyses with Trx-h2 and Trx-h3. In Arabidopsis thaliana, h-type Trxs are categorized into three subgroups based on their N-terminal extensions and lipid modification. Sub-III Trx-h9 comprises 140 amino acids, including the canonical redox-active motif WCGPC. In addition, Trx-h9 has a N-terminal region containing lipid modification sites for myristoylation and palmitoylation. To elucidate its molecular functions, recombinant Trx-h9 was assayed for disulfide reductase activity (via insulin reduction assay), molecular chaperone capacity (assessed as holdase activity), and nucleic acid-binding specificity. Trx-h9 exhibited concentration-dependent insulin disulfide reductase activity, although its catalytic efficiency was lower than that of Trx-h2 and Trx-h3. Moreover, Trx-h9 displayed molecular chaperone activity similar to that observed in Trx-h3. DNA binding assays further revealed that Trx-h9 preferentially binds double-stranded DNA compared with single-stranded DNA. These multifunctional characteristics imply that Trx-h9 operates as a versatile protein, integrating disulfide reductase activity with holdase chaperone capacity and DNA-binding properties. The coupling of these activities suggests roles in both protein redox regulation and maintenance of macromolecular stability during cellular stress responses.
BCL2L10 Is a non-GCB-associated prognostic biomarker and functional driver in diffuse large B-Cell lymphoma.
Yu L, Wu S, Li L … +4 more , Yang J, Man J, Song F, Zhao L
Biochem Biophys Res Commun · 2026 Aug · PMID 42202531 · Publisher ↗
Diffuse large B-cell lymphoma (DLBCL) is characterized by marked heterogeneity between GCB and non-GCB subtypes. Here, we identified BCL2L10 as a non-GCB-specific oncogene through integrated bioinformatics, clinical vali...
Diffuse large B-cell lymphoma (DLBCL) is characterized by marked heterogeneity between GCB and non-GCB subtypes. Here, we identified BCL2L10 as a non-GCB-specific oncogene through integrated bioinformatics, clinical validation, and functional assays. BCL2L10 was significantly upregulated in non-GCB DLBCL at both mRNA and protein levels. High BCL2L10 expression served as an independent adverse prognostic factor and correlated with advanced clinical stage. Gene set enrichment analysis linked BCL2L10 to biosynthetic and stress-response pathways. Functional assays demonstrated that BCL2L10 knockdown selectively suppressed proliferation in non-GCB DLBCL cells, whereas overexpression only mildly promoted GCB cell growth. Our findings identify BCL2L10 as a novel subtype-specific prognostic biomarker and therapeutic target for high-risk non-GCB DLBCL.
Satb1 enforces CD4 effector T cell lineage stability by repressing Foxp3 via DNA methylation.
Seo W, Zou C, Nair K … +4 more , Koseki H, Kohwi-Shigematsu T, Nishikawa H, Taniuchi I
Biochem Biophys Res Commun · 2026 Aug · PMID 42202530 · Publisher ↗
Special AT-rich sequence binding protein 1 (Satb1) is a critical chromatin organizer that globally regulates the T lymphocyte transcriptome. While its influence on primary T cell development is well documented, defining...
Special AT-rich sequence binding protein 1 (Satb1) is a critical chromatin organizer that globally regulates the T lymphocyte transcriptome. While its influence on primary T cell development is well documented, defining its specific function in mature peripheral T cells has been complicated by the developmental defects inherent to early-stage deletion models. To bypass these limitations, we utilized a Thpok-cre conditional knockout system to delete Satb1 specifically within mature CD4 single-positive thymocytes. We demonstrate that the ablation of Satb1 results in the spontaneous emergence of an atypical CD25FoxP3 population from naïve peripheral CD4 T cells. This aberrant de-repression of Foxp3 occurs independently of TGFβ signaling and is fundamentally driven by alterations in DNA methylation, requiring the activity of the TET2 and TET3 demethylases. Furthermore, we show that this Satb1-deficient Foxp3 expression is unstable during in vitro activation and is insufficient to confer full regulatory T cell (Treg) functionality. Collectively, our findings reveal a critical requirement for Satb1 in enforcing the lineage stability and functional fitness of conventional CD4 T cells by maintaining the epigenetic silencing of Foxp3, providing vital insights into T cell homeostasis.
Electroneutral Na-Cl cotransport activity of anguillid eel Slc12a10 expressed in Xenopus oocytes.
Ota C, Kato A
Biochem Biophys Res Commun · 2026 Aug · PMID 42202529 · Publisher ↗
Slc12a10 is a homolog of the Na-Cl cotransporter Ncc (Slc12a3) and is also referred to as Nccβ or Ncc2. The Slc12a10 gene is widely distributed among bony vertebrates; however, it has been lost or pseudogenized in birds,...
Slc12a10 is a homolog of the Na-Cl cotransporter Ncc (Slc12a3) and is also referred to as Nccβ or Ncc2. The Slc12a10 gene is widely distributed among bony vertebrates; however, it has been lost or pseudogenized in birds, most mammals including humans, and some teleost fishes. Slc12a10 is expressed in the intestinal epithelium of anguillid eels and in ionocytes of the zebrafish gill, where it is thought to contribute to epithelial NaCl transport. Despite these observations, only a limited number of studies have directly evaluated the transport activity of Slc12a10, and its ion-coupling properties and electrical characteristics remain incompletely defined. To address this gap, we examined the transport activity of Slc12a10 from European and Japanese eels (Anguilla anguilla and Anguilla japonica) using a Xenopus laevis oocyte expression system combined with ion-selective microelectrode measurements. When oocytes expressing eel Slc12a10 were exposed to Na-free solution, intracellular Na and Cl activities decreased significantly. Similar decreases in intracellular Na and Cl activities were observed upon exposure to Cl-free solution. These changes were not observed in control oocytes and were not accompanied by significant changes in membrane potential. Furthermore, under voltage-clamp conditions at -20 mV, exposure of Slc12a10-expressing oocytes to Na-free solution induced a significant decrease in intracellular Na activity without generating detectable membrane currents. These activities were comparable to those previously reported for zebrafish Slc12a10.1. Together, these results provide new evidence that eel Slc12a10 functions as an electroneutral Na-Cl cotransporter and suggest that this transport mechanism is conserved across fish species.
Preconditioning and supplementation with glutathione ameliorates oxidative stress, mitochondrial dysfunction, and restores metabolic imbalance in insulin-resistant myotubes.
Save SN, Parveen N, Sonis G … +3 more , Chavan S, Chugh J, Sharma S
Biochem Biophys Res Commun · 2026 Aug · PMID 42202436 · Publisher ↗
Insulin resistance, defined as the inability of the insulin-target tissues including skeletal muscles to insulin action, has been identified as a major pathophysiology associated with the development of metabolic disorde...
Insulin resistance, defined as the inability of the insulin-target tissues including skeletal muscles to insulin action, has been identified as a major pathophysiology associated with the development of metabolic disorders including type 2 diabetes mellitus. Palmitic acid (PA) and related saturated free fatty acids contribute significantly to the development of insulin resistance by perturbing the redox homeostasis in the cells. The deficiency of the intracellular antioxidant - glutathione (GSH) has been documented in insulin-resistant states, and dietary supplementation of GSH and its precursors has been associated with the alleviation of oxidative stress, restoration of intra-abdominal fat levels, enhancement of insulin sensitivity and glucose metabolism. However, the key metabolic pathways targeted by GSH in mediating this protection need to be identified so that they can be targeted for effective management of insulin resistance. In this study, we aimed to elucidate whether preconditioning and supplementation with GSH (0.1 and 1 mM) could alleviate the oxidative stress, mitochondrial dysfunction, and metabolic perturbations induced by PA in the L6 skeletal myotubes. Metabolic perturbations associated with the same were identified using H NMR spectroscopy. It was observed GSH supplementation at concentrations of 1 mM in the myotubes experiencing lipotoxicity led to the partial restoration of metabolic imbalances observed in levels of nucleotides (UMP, adenosine, AMP), GSH metabolism intermediates (glutamine, pyroglutamate), acetate, amino acids including proline, aspartate, threonine; phospholipid intermediates (o-phosphocholine, choline), niacinamide, TCA cycle intermediates (citrate), and glycerol. Thus, we believe that these metabolic pathways can be targeted for the management of lipotoxicity and insulin resistance.
Leveraging CRISPR/Cas9 for optimized adoptive T cell therapies: From molecular engineering to clinical manufacturing.
Kim JH, Cho HJ, Lee HM
Biochem Biophys Res Commun · 2026 Aug · PMID 42190604 · Publisher ↗
Cancer immunotherapy is rapidly evolving from pharmacologic immune modulation to adoptive cell therapy (ACT). In ACT, T cells are expanded and genetically engineered ex vivo to achieve long-lasting antitumor activity. Th...
Cancer immunotherapy is rapidly evolving from pharmacologic immune modulation to adoptive cell therapy (ACT). In ACT, T cells are expanded and genetically engineered ex vivo to achieve long-lasting antitumor activity. The primary ACT platforms-tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR) T cells, and T-cell receptor (TCR) T cells-rely on T-cell effector function but differ in their mechanisms of antigen recognition, HLA dependence, and engineering requirements, leading to unique clinical strengths and limitations. CRISPR/Cas9 genome editing provides precise knock-out (KO) and knock-in (KI) strategies, allowing for multiplex editing and functional modulation across the genome. In the context of ACT manufacturing, CRISPR/Cas9 addresses critical challenges such as T-cell exhaustion, graft-versus-host disease (GvHD), and ensuring product consistency and quality. This article explores how CRISPR/Cas9 can be utilized to overcome the limitations of ACT and summarizes the current clinical landscape of CRISPR-engineered ACT products. Finally, we discuss the ongoing challenges associated with CRISPR-based genome editing and propose potential solutions.
Dual proximity-based interactome mapping of FKBP51 and FKBP52 uncovers shared metabolic networks.
Hill SE, Parikh P, Gebru NT … +5 more , Banjade S, Guergues J, Wohlfahrt J, Stevens SM, Blair LJ
Biochem Biophys Res Commun · 2026 Aug · PMID 42190603 · Publisher ↗
The 51 kDa FK506-binding protein (FKBP51) has been studied for its involvement in regulating multiple biological systems, particularly as a regulator of steroid hormone receptors, but roles in metabolism, pain response,...
The 51 kDa FK506-binding protein (FKBP51) has been studied for its involvement in regulating multiple biological systems, particularly as a regulator of steroid hormone receptors, but roles in metabolism, pain response, cell survival, protein turnover, autophagy, immune response, and insulin signaling have also been described. Genetic variants of FKBP51 are associated with various stress-related mental disorders. While recent research has clarified aspects of these processes, the complete range of FKBP51 interactions remains undetermined. FKBP52, a closely related homolog, also affects similar pathways. Recent studies have identified new protein partners for FKBP51 and FKBP52, suggesting an even broader interactome with transient associations. To further characterize interactions, TurboID-based proximity labeling was performed in HeLa cells. Proteomic analysis confirmed known FKBP51 and FKBP52 interactions, while also identifying additional shared and unique binding partners with strong enrichment in metabolic pathways, amino acid biosynthesis, and carbon metabolism. Although FKBP51 and FKBP52 proximal proteins were primarily cytosolic, FKBP51 showed additional associations with exosomal proteins while FKBP52 engaged with additional nuclear proteins. These findings highlight the overlapping roles in metabolic signaling and differentiate pathway-specific partners.
Fueling death: Glucose metabolic reprogramming regulates ferroptosis and cuproptosis in cancer.
Zhang Y, Chen Z, Li K … +1 more , Zhu Q
Biochem Biophys Res Commun · 2026 Aug · PMID 42190602 · Publisher ↗
Reprogramming of glucose metabolism is a hallmark of cancer that not only fuels tumor growth but also profoundly regulates cell fate by modulating susceptibility to metal-dependent cell death. This review systematically...
Reprogramming of glucose metabolism is a hallmark of cancer that not only fuels tumor growth but also profoundly regulates cell fate by modulating susceptibility to metal-dependent cell death. This review systematically delineates the mechanistic landscape through which tumor glucose metabolic reprogramming governs ferroptosis and cuproptosis, two emerging forms of regulated cell death driven by iron and copper, respectively. We highlight that glucose metabolism functions as a shared upstream hub, wherein distinct metabolic branches-including glycolysis, the pentose phosphate pathway, the hexosamine biosynthesis pathway, and lactate metabolism-differentially sculpt cellular vulnerability to these death modalities. In ferroptosis, these pathways converge on the NADPH-GSH-GPX4 axis to reinforce antioxidant capacity and lipid remodeling, thereby elevating the ferroptotic threshold. Conversely, cuproptosis sensitivity is dictated by mitochondrial oxidative metabolism and the availability of lipoylated TCA cycle proteins, both of which are suppressed under glycolysis-dominant states. We further discuss how tumor microenvironmental factors, particularly acidification, modulate cuproptosis execution and therapeutic response. Finally, we review emerging therapeutic strategies that leverage metabolic intervention, nanoplatform-based delivery, and combination therapies to exploit these vulnerabilities. By framing glucose metabolism as a central metabolic shunt that regulates the balance between ferroptosis and cuproptosis, this review provides a unified framework for understanding metal-dependent cell death in cancer and offers a roadmap for developing metabolism-targeted combination therapies.
Cilostazol inhibits TGF-α-induced migration of hepatocellular carcinoma cells by activating PPARγ.
Matsushima-Nishiwaki R, Tokuda H, Kozawa O
Biochem Biophys Res Commun · 2026 Aug · PMID 42190601 · Publisher ↗
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and remains a public health problem with high mortality. We have previously reported that activation of cyclic adenosine monophosphate (cAMP)-dep...
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and remains a public health problem with high mortality. We have previously reported that activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) suppresses transforming growth factor (TGF)-α-induced migration of HCC cells. In the present study, we investigated whether cilostazol, a phosphodiesterase (PDE) inhibitor, affects the TGF-α-induced migration of HCC cells. Cilostazol significantly inhibited TGF-α-induced migration of human-derived HCC cells, HuH7. Dipyridamole, another PDE inhibitor, also significantly suppressed the cell migration induced by TGF-α. However, neither cilostazol nor dipyridamole increased the intracellular concentrations of cAMP under TGF-α-stimulation. Furthermore, TGF-α-induced HCC cell migration, which was inhibited by cilostazol and dipyridamole, was not affected by a PKA inhibitor. On the other hand, cilostazol and dipyridamole stimulated the activation of peroxisome proliferator-activated receptor γ (PPARγ) in HuH7 cells. We also found that PPARγ activators, ciglitazone and pioglitazone, significantly inhibited the TGF-α-induced migration of HuH7 cells. The inhibitory effects of cilostazol and dipyridamole on the migration of HuH7 cells were blocked by GW9662, an inhibitor of PPARγ. We have shown that AKT is involved in the TGF-α-induced HuH7 cell migration. The PPARγ activators reduced the TGF-α-induced AKT activation without affecting the EGFR activation. Cilostazol and dipyridamole also inhibited the activation of AKT but not EGFR. Taken together, these results strongly suggest that cilostazol and dipyridamole inhibit TGF-α-induced HCC cell migration by suppressing the AKT pathway through PPARγ activation.
Corrigendum to "Overexpression of Dentin matrix protein 1 in Nestin+ cells causes bone loss in mouse long bone" [Biochem. Biophys. Res. Communications 490 (2017) 356-363].
Pan M, Weng Y, Sun Y
Biochem Biophys Res Commun · 2026 Aug · PMID 42185190 · Publisher ↗
Abstract loading — click title to view on PubMed.
Periodontal ligament stem cell-derived exosomal miR-378a programs osteogenic commitment via DAZAP2/SMAD signaling.
Gao J, Liu A, Iwata T
Biochem Biophys Res Commun · 2026 Aug · PMID 42185189 · Publisher ↗
Functional recovery of the periodontium remains a major clinical challenge. To harness the therapeutic potential of extracellular vesicles (EVs) derived from human periodontal ligament mesenchymal stem cells (hPDL-MSC),...
Functional recovery of the periodontium remains a major clinical challenge. To harness the therapeutic potential of extracellular vesicles (EVs) derived from human periodontal ligament mesenchymal stem cells (hPDL-MSC), we identified and characterized the encapsulated miR-378a as a pivotal regulator associated with osteogenic commitment. hPDL-MSC and derivative EVs were dynamically examined throughout osteogenesis, revealing a temporal and progressive enrichment pattern. Mechanistically, integrative microarray, RNA sequencing, bioinformatic analysis, and functional assays established PIM2 and DAZAP2 as direct targets of miR-378a. Overexpression of miR-378a post-transcriptionally suppressed DAZAP2, leading to enhanced nuclear translocation of phosphorylated-SMAD1/5/9 and subsequent activation of canonical BMP signaling. Rescue experiments reinforced the essential role of the miR-378a-DAZAP2-SMAD axis in osteogenic differentiation. Collectively, our findings delineate the molecular pathway triggered by hPDL-MSC-derived exosomal miR-378a and provide new mechanistic insights into EV-mediated modulation of stem cell fate.
IL-27 blockade suppresses IL-10 modification in Th1 cells and promotes intracranial aneurysms rupture.
Zeng X, Zang F, Bu G … +5 more , Yang Y, Fan H, Qiu R, Yuan D, Zhou L
Biochem Biophys Res Commun · 2026 Aug · PMID 42184471 · Publisher ↗
Intracranial aneurysms (IA) stability is regulated by helper T (Th)-cell homeostasis, but the role of IL-27, a key cytokine inducing regulatory T-cell phenotypes, remains unexplored. This study aimed to determine the rol...
Intracranial aneurysms (IA) stability is regulated by helper T (Th)-cell homeostasis, but the role of IL-27, a key cytokine inducing regulatory T-cell phenotypes, remains unexplored. This study aimed to determine the role of IL-27 insufficiency in IA rupture and to elucidate the underlying immunopathological mechanisms. We integrated transcriptomic data from human IA tissues with an elastase-induced hypertensive mouse model. Findings were gained through IL-27 blockade in vivo, immunofluorescence staining, and in vitro co-culture systems involving bone marrow-derived macrophages (BMDMs) with IL-27 blockade, CD4 T cells, and cerebrovascular endothelial system. IL-27 expression was markedly reduced in ruptured human and mouse IA tissues. In mice, IL-27 blockade increased the IA rupture rate, exacerbated vascular remodeling, and promoted endothelial injury. This was accompanied by a systemic inflammatory shift, with decreased IL-10 and increased IFN-γ levels, alongside localized expansion of T-bet Th1 cells and depletion of IL-10 type 1 regulatory T (Tr1) cells in IA wall. Although CD68 macrophages abundantly infiltrated IA lesions, their IL-27 production was impaired. In vitro IL-27 blockade in BMDMs promoted Th1 polarization, suppressed Tr1 differentiation, and rendered CD4 T cells capable of inducing endothelial damage and soluble adhesion molecule release. IL-27 blockade promotes IA rupture by disrupting Th1/Tr1 balance, which may through impaired macrophage function, revealing a novel immunopathological mechanism and potential therapeutic target for IA management.
Human PRSS8 functions as a targetable, endogenous TGFBR3 sheddase via the novel cholesterol-PRSS8-TGF-β axis.
Greulich BM, Post J, Pawlak J … +9 more , Eidson K, Fitzgibbons H, Garver R, Karas E, Kim C, Lam H, Sudakar S, Teng E, Blobe GC
Biochem Biophys Res Commun · 2026 Aug · PMID 42184470 · Publisher ↗
Many cancers display dysregulation of the TGF-β pathway, which can produce a myriad of oncogenic phenotypes including evasion of the immune system, epithelial to mesenchymal transition, metastasis, and angiogenesis. As s...
Many cancers display dysregulation of the TGF-β pathway, which can produce a myriad of oncogenic phenotypes including evasion of the immune system, epithelial to mesenchymal transition, metastasis, and angiogenesis. As such, this pathway has been of much interest when trying to design new therapeutic options. Unfortunately, these attempts to inhibit TGF-β have had very limited success, likely because of the critical roles that TGF-β plays in the normal tissues of the body. For this reason, the work here aimed to more fully understand the regulation of TGF-β signaling with a long-term goal of restoring normal TGF-β signaling by manipulating these regulatory events. The co-receptor TGFBR3 can promote TGF-β signaling when bound to the cell surface. However, this co-receptor can also be shed from the membrane and inhibit signaling. The enzyme responsible for TGFBR3 shedding and the regulatory mechanisms controlling this process remain poorly characterized. Here, PRSS8 was identified to be an endogenous sheddase of TGFBR3, and the expression of PRSS8 had functional impacts on phenotypes mediated by TGF-β signaling. Furthermore, PRSS8, and therefore TGF-β signaling, can be regulated by cholesterol homeostasis pathways. This establishes for the first time a cholesterol-PRSS8-TGF-β signaling axis that could provide novel therapeutic options for cancers experiencing dysregulated TGF-β signaling.
Deciphering the multi-target mechanism of Magnolia officinalis in irritable bowel syndrome with diarrhea: A combined network pharmacology, machine learning, and in vivo validation study.
Wang X, Wei Y, Wang M … +5 more , Zhang Y, Liu L, Ma X, Gao L, Ji H
Biochem Biophys Res Commun · 2026 Aug · PMID 42176387 · Publisher ↗
BACKGROUND: The bark of Magnolia officinalis Rehder & E. Wilson, used in TCM for abdominal distension, pain, and diarrhea, aligns with IBS-D symptoms. It is now supported by evidence for its multi-component, multi-target...
BACKGROUND: The bark of Magnolia officinalis Rehder & E. Wilson, used in TCM for abdominal distension, pain, and diarrhea, aligns with IBS-D symptoms. It is now supported by evidence for its multi-component, multi-target action. This study aims to elucidate the core bioactive components and their mechanisms against IBS-D. To achieve this, we employed an analytical strategy that uses machine learning to refine network pharmacology predictions, rather than relying on network pharmacology alone. MATERIALS AND METHODS: This study integrates network pharmacology and machine learning to identify core therapeutic targets. The affinity of the components for these targets is validated through molecular docking studies. An IBS-D rat model was used to evaluate the effects of the core components (magnolol, honokiol, obovatol) on behavior (sucrose preference, open field), gastrointestinal motility, intestinal permeability, serum inflammatory cytokines (ELISA), and core target gene expression (qRT-PCR). RESULTS: Computational analyses identified five potential active components, including magnolol (Mag), honokiol (Hnk), and obovatol (Obo), and eight core targets (e.g., EGFR, MET) involved in PI3K-Akt and FoxO pathways. Molecular docking confirmed stable binding. In vivo, Hnk, Mag, and Obo ameliorated IBS-D-related anxiety-like behavior, intestinal hypermotility, and barrier dysfunction. They significantly downregulated EGFR and MET expression and reduced serum levels of IL-8, TNF-α, and MyD88. Notably, all treatments increased fecal short-chain fatty acids (SCFAs). CONCLUSION: The core components of M. officinalis, represented by Hnk, Mag, and Obo, alleviate IBS-D likely through a multi-target mechanism involving suppression of EGFR/MET and subsequent PI3K-Akt signaling, leading to reduced inflammation, improved barrier function, and modulated gut-brain axis. This provides a mechanistic foundation for the traditional use of M. officinalis in treating gastrointestinal disorders.
Adrenocorticotropin hormone regulates sphingosine-1-phosphate synthesis via cortisol in bovine adrenocortical cells.
Medina-Moctezuma ZB, Guzmán-Sánchez A, González-Aretia D … +3 more , Gutiérrez CG, Hernández-Coronado CG, Rosales-Torres AM
Biochem Biophys Res Commun · 2026 Aug · PMID 42176386 · Publisher ↗
Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) stimulate the synthesis of sphingosine-1 phosphate (S1P) in Gs-coupled receptors dependent manner, enabling S1P to mediate specific bioactivities of FSH and...
Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) stimulate the synthesis of sphingosine-1 phosphate (S1P) in Gs-coupled receptors dependent manner, enabling S1P to mediate specific bioactivities of FSH and LH. Because adrenocorticotropic hormone (ACTH) also acts via a Gs-coupled receptor to regulate adrenal cortex function, we hypothesized that ACTH could induce S1P secretion in adrenocortical cells, which could then mediate the steroidogenic and number of viable cells effects associated with ACTH. Primary bovine adrenocortical cell cultures were treated with ACTH, and number of viable cells, as well as S1P and cortisol concentrations in the culture media were measured. The effects of exogenous cortisol on number of viable cells, S1P and phosphorylated SPHK1 concentrations were also determined. Results show that the addition of 0.001 μM and 0.1 μM ACTH to the culture medium increased the number of viable adrenocortical cells, and the concentration of cortisol in culture media, respectively. However, ACTH addition did not increase S1P concentrations. Interestingly, a negative correlation between S1P and cortisol concentrations in the culture medium was observed. Moreover, while addition of 0.1 ng/mL cortisol increased S1P and phosphorylated SPHK1 concentrations, increasing cortisol from 1 to 10 ng/mL did not affect phosphorylated SPHK1 but reduced S1P concentration. Thus, while our data suggest that ACTH does not promote S1P synthesis; by stimulating cortisol synthesis, ACTH could be involved in regulation of S1P levels in bovine adrenocortical cells.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe